Racemic bupivacaine, a long-acting local anaesthetic, is useful in chronic administration as an analgesic in some pain syndromes. However, racemic bupivacaine is cardiotoxic, having depressant electrophysiological and mechanical effects on the heart. It should therefore be used with caution in cardiac-compromised patients.
It is known that levobupivacaine is probably less cardiotoxic than dexbupivacaine and racemic bupivacaine. See, for example, Vanhoutte et al, Br. J. Pharmacol. 103:1275-1281 (1991), and Denson et al, Regional Anaesthesia, 17:311-316 (1992). Vanhoutte et al studied the effects of bupivacaine enantiomers on the electrophysiological properties of guinea pig isolated papillary muscle; this is based on their statement that "the cardiotoxicity of bupivacaine seems to be mainly of electrophysiological origin".
Berrisford et al, Br. J. Anaesthesia 70:201-204 (1993), disclose the administration of bupivacaine and its enantiomers during continuous extrapleural intercostal nerve block, as an analgesic for patients who have undergone thoracotomy. The infusion of bupivacaine was maintained until the morning of the fifth day after operation.
Du Pen et al, Pain 49:293-300 (1992), report the use of chronic epidural and opioid infusions in concentrations between 0.1 and 0.5% bupivacaine in intractable cancer pain. The median length of therapy was 60-120 days, with the longest infusion lasting 277 days. A progressive reduction in bupivacaine clearance was reported.
Cardiotoxicity is not usually a clinical problem at low single doses, e.g. by use in epidurals and nerve blockade. However, for chronic administration, the myocardium may have to withstand the possible cumulative cardiotoxic side-effects of the local anaesthetic.
Pain has been classified, by the WHO Analgesic Ladder; see also the review by Ashburn and Lipman, "Management of Pain in the Cancer Patient". At the first step of the ladder, of mild to moderate pain, treatment with a non-opioid.+-.adjuvant is required. If pain persists. or increases, treatment should be with an opioid for mild to moderate pain, plus non-opioid.+-.adjuvant. If pain persists or increases beyond this second step, an opioid for moderate to severe pain is required, with or without non-opioid and/or adjuvant. Cancer and post-operative pain is typically of this third step.
An individual can be at any step on this ladder of pain at any time. Patents with acute pain will tend to go down the ladder with time; patients with chronic pain or malignancy may "climb the ladder" with time, increasingly potent analgesics then being required to control the worsening pain associated with progression of the disease.